Hagen Anne I, Bofin Anna M, Ytterhus Borgny, Maehle Lovise O, Kjellevold Kjell H, Myhre Hans O, Møller Pål, Lønning Per E
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
Acta Oncol. 2007;46(2):199-203. doi: 10.1080/02841860600949552.
BRCA1 associated tumours are found to express an oestrogen receptor negative "basal epithelial-like" phenotype. In contrast to ER negative tumours in general, such tumours rarely harbour amplification of the HER-2 gene. However, little is known about TOP2A gene amplification status in BRCA1-associated tumours. Such information may be of importance to therapy, as amplification of TOP2A has been associated with dose-dependent sensitivity to anthracycline therapy in breast cancer. We examined 40 breast carcinomas from BRCA1 mutation carriers and 40 sporadic breast carcinomas matched for age, tumour diameter and histological grade for HER-2 and TOP2A amplification status using fluorescence in situ hybridisation (FISH). Co-amplification of TOP2A and HER-2 was found in four of the mutation carriers and in three of the controls. While six tumours in the control group harboured HER-2 amplifications with normal TOP2A, this occurred in three of the BRCA1 associated tumours only. In contrast, three of the BRCA1-associated tumours but none of the controls harboured TOP2A amplification despite normal HER-2 status. Our findings have potential therapeutic implications. HER-2 assessment is routinely used to select breast cancer patients for trastuzumab but also dose-intensive anthracycline therapy. Our data suggest that BRCA1-associated breast cancers also need to be tested for TOP2A amplification.
研究发现，与BRCA1相关的肿瘤表现出雌激素受体阴性的“基底上皮样”表型。与一般的雌激素受体阴性肿瘤不同，此类肿瘤很少出现HER-2基因扩增。然而，对于BRCA1相关肿瘤中TOP2A基因的扩增状态，人们了解甚少。此类信息对于治疗可能具有重要意义，因为TOP2A的扩增与乳腺癌中蒽环类药物治疗的剂量依赖性敏感性相关。我们使用荧光原位杂交（FISH）技术，检测了40例BRCA1突变携带者的乳腺癌以及40例年龄、肿瘤直径和组织学分级相匹配的散发性乳腺癌的HER-2和TOP2A扩增状态。在4例突变携带者和3例对照者中发现了TOP2A和HER-2的共扩增。对照组中有6例肿瘤存在HER-2扩增但TOP2A正常，而在BRCA1相关肿瘤中只有3例出现这种情况。相反，3例BRCA1相关肿瘤存在TOP2A扩增但HER-2状态正常，而对照组中无一例出现这种情况。我们的研究结果具有潜在的治疗意义。HER-2评估通常用于选择接受曲妥珠单抗治疗以及剂量密集型蒽环类药物治疗的乳腺癌患者。我们的数据表明，BRCA1相关的乳腺癌也需要检测TOP2A扩增情况。
